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  • Title: Cationic nanosystems for the delivery of small interfering ribonucleic acid therapeutics: a focus on toxicogenomics.
    Author: Akhtar S.
    Journal: Expert Opin Drug Metab Toxicol; 2010 Nov; 6(11):1347-62. PubMed ID: 20929276.
    Abstract:
    IMPORTANCE OF THE FIELD: siRNAs may serve as novel nanomedicines for sequence-specific gene silencing in the clinic. However, delivering siRNA to targeted tissue or cells remains a challenge. An appropriate delivery nanosystem such as cationic polymers or liposomes is required for effective gene silencing with siRNA in vivo but the available drug delivery vectors are not all biologically inert. AREAS COVERED IN THIS REVIEW: A combination of highly focused and comprehensive literature searches to identify any relevant reports using Medline (from 1950 to 7 April 2010) through the OVID system. WHAT THE READER WILL GAIN: Using cationic delivery nanosystems as examples, this review article highlights the importance of undertaking toxicogenomics studies - the application of transcription profiling to toxicology - to acquire gene expression signatures of siRNA delivery systems so as to determine and/or predict their impact on gene silencing activity and specificity. Such nanotoxicological information will be important for the optimal selection of siRNA-delivery system combinations in the many proposed clinical applications of RNA interference. TAKE HOME MESSAGE: Cationic delivery nanosystems can elicit multiple gene expression changes in cells that may contribute to the 'off-target' effects of siRNAs and/or modulate their pharmacological activity. Thus, selection of delivery systems for siRNA applications should be based on both their delivery enhancing capability and toxicogenomics.
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